title: Immunogenicity of ALVAC-HIV vCP1521 in infants of HIV-1-infected women in Uganda (HPTN 027): the first pediatric HIV vaccine trial in Africa.
abstract: OBJECTIVE
  Maternal-to-child-transmission of HIV-1 infection remains a significant cause of HIV-1 infection despite successful prevention strategies. Testing protective HIV-1 vaccines remains a critical priority. The immunogenicity of ALVAC-HIV vCP1521 (ALVAC) in infants born to HIV-1-infected women in Uganda was evaluated in the first pediatric HIV-1 vaccine study in Africa.
  
  
  METHODS
  HIV Prevention Trials Network 027 was a randomized, double-blind, placebo-controlled phase I trial to evaluate the safety and immunogenicity of ALVAC in 60 infants born to HIV-1-infected mothers with CD4 counts of >500 cells per microliter, which were randomized to the ALVAC vaccine or placebo. ALVAC-HIV vCP1521 is an attenuated recombinant canarypox virus expressing HIV-1 clade E env, clade B gag, and protease gene products.
  
  
  METHODS
  Infants were vaccinated at birth and 4, 8, and 12 weeks of age with ALVAC or placebo. Cellular and humoral immune responses were evaluated using interferon-γ enzyme-linked immunosorbent spot, carboxyfluorescein diacetate succinimidyl ester proliferation, intracellular cytokine staining, and binding and neutralizing antibody assays. Fisher exact test was used to compare positive responses between the study arms.
  
  
  RESULTS
  Low levels of antigen-specific CD4 and CD8 T-cell responses (intracellular cytokine assay) were detected at 24 months (CD4-6/36 vaccine vs. 1/9 placebo; CD8-5/36 vaccine vs. 0/9 placebo) of age. There was a nonsignificant trend toward higher cellular immune response rates in vaccine recipients compared with placebo. There were minimal binding antibody responses and no neutralizing antibodies detected.
  
  
  CONCLUSIONS
  HIV-1-exposed infants are capable of generating low levels of cellular immune responses to ALVAC vaccine, similar to responses seen in adults.
authors.affiliation: *Medical Research Council/Uganda Virus Research Institute, Entebbe, Uganda; †SCHARP, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; ‡Viral and Rickettsial Disease Laboratory, Richmond, CA; §Joint Clinical Research Center, Kampala, Uganda; ‖Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; ¶Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda; #Department of Paediatrics and Child Health, College of Health Sciences, Makerere University, Kampala, Uganda; **George Washington University School of Public Health and Health Services, Washington, DC; ††FHI 360, Durham, NC; and ‡‡Sanofi Pasteur, Discovery Drive, Swiftwater, PA.
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.forename: Harr Freeya
authors.initials: HF
authors.lastname: Njai
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Norman
authors.initials: N
authors.lastname: Jones
authors.forename: Isaac
authors.initials: I
authors.lastname: Ssewanyana
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kintu
authors.forename: Lynda
authors.initials: L
authors.lastname: Emel
authors.forename: Philippa
authors.initials: P
authors.lastname: Musoke
authors.forename: Mary Glenn
authors.initials: MG
authors.lastname: Fowler
authors.forename: San-San
authors.initials: SS
authors.lastname: Ou
authors.forename: J Brooks
authors.initials: JB
authors.lastname: Jackson
authors.forename: Laura
authors.initials: L
authors.lastname: Guay
authors.forename: Philip
authors.initials: P
authors.lastname: Andrew
authors.forename: Lynn
authors.initials: L
authors.lastname: Baglyos
authors.forename: Huyen
authors.initials: H
authors.lastname: Cao
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000097:blood; D049109:Cell Proliferation; D002675:Child, Preschool; D004311:Double-Blind Method; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D011247:Pregnancy; D016896:Treatment Outcome; D014454:Uganda; D014611:Vaccination / Q000009:adverse effects* / Q000379:methods*
chemical_list: D016915:AIDS Vaccines; C112734:AIDSVAX; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D010919:Placebos; D007371:Interferon-gamma